The suppression or dysregulation of the immune system can be a component of many pathological diseases or conditions. In particular, immune dysregulation can result in the onset and progression of disease. Where onset of disease occurs, the dysregulation of the immune system means that an individual is compromised against mounting a full immune response against a particular disease or pathogenic condition.
Acute Radiation Syndrome (ARS) results from the exposure of an individual to a high level of radiation. ARS is a life threatening condition, primarily due to the depletion in the blood cell count. High levels of radiation inhibits production of blood cells by the bone marrow. Such blood cells include; white blood cells, neutrophils, platelets and factors required for blood clotting. Severe depletion of these blood components results in conditions such as neutropenia, where a low neutrophil count is present and thrombocytopenia where there is a low platelet count.
Although the bone marrow can functionally revert to produce blood cell components at the level produced prior to radiation exposure, this reversion can take up to 3 months. In the interim, the immune system is severely compromised due to the depletion in cell numbers, and in particular due to a depleted neutrophil count.
With the possibility of a terrorist attack which would include, in some form, a radioactive element, there is the need for viable treatments to ARS which are cost effective and which are easy to produce and administer, and which have previous human use for other indications.
Chemotherapy can also cause damage to bone marrow and accordingly result in a decrease in neutrophil and platelet count. Again, the use of compounds which could be administered to reduce the side effects of chemotherapy on bone marrow cell production would be highly desirable.
The inventor of the present invention has surprisingly identified two groups of compounds which have been unexpectedly shown to mediate, either on their own, or in combination with other compounds, a protective effect against blood cell depletion. Preventing blood cell depletion can mediate the remission of neutropenia, thrombocytopenia and anaemia, and can also stimulate an enhancement of B cell and T cell function, following such function being compromised due to exposure of a subject to radiation.
The compounds identified by the inventor are non steroidal compounds, which have been unexpectedly shown to have utility in the treatment and/or amelioration of one or more condition which can be attributed to a deficiency or dysregulation in blood cell number, and in particular of the function of the immune system. This dysregulation is particularly characterised by a reduction in a reduction in a number of cells, such as lymphocytes which have a role or function in mediating immunity. As such, the compounds of the present invention have utility in methods for the treatment of immuno-suppressive conditions mediated by exposure to radiation, and in particular to blood cell deficiencies such as neutropenia and thrombocytopenia.